tbuckley/cabot-search huggingface dataset:
Clinical characteristics and real-world progression-free survival (rwPFS) of patients with HER2-positive and hormone receptor (HR)-positive metastatic breast cancer (MBC) initiating endocrine therapy (ET) in combination with the first line of treatment: An analysis of electronic health records in the United States.
Authors: Thibaut Sanglier, Jinjoo Shim, Daniel Eiger, Raf Poppe, Eleonora Restuccia
Journal: Journal of Clinical Oncology (2022)

e13028 Background: Dual HER2 blockade with pertuzumab (P) + trastuzumab (H), combined with taxane induction therapy, is the standard of care for the first-line treatment of patients with HER2-positive MBC. In clinical practice, after achieving clinical benefit with approximately 4–6 cycles of PH + taxane induction, maintenance therapy is continued with PH only until disease progression or unmanageable toxicity. Approximately 50–60% of patients with HER2-positive MBC also have concurrent HR expression and may receive ET in combination with PH. This study investigated the clinical characteristics and outcomes of patients initiating ET combined with PH as maintenance therapy after completion of PH + taxane induction. Methods: We conducted a retrospective cohort study using a nationwide US electronic health record-derived de-identified database (Flatiron Health). Patients with HER2-positive and HR-positive MBC who initiated an ET between Jan 1, 2012 and Feb 28, 2021 with concomitant PH after receiving at least four cycles of first-line PH + taxane induction were included. The index date was the date of ET initiation. Progression data were abstracted from the medical charts. Mortality data were abstracted and combined with patient-level structured data (obituaries and Social Security Death Index). rwPFS was defined as the time from index date until first progression event &gt; 14 days after the index date, or date of death; otherwise, patients were censored on the date of last clinical note abstraction. Baseline characteristics were described using summary statistics, and rwPFS in the maintenance setting was described using a Kaplan–Meier estimator from the index date. Results: Of 24,690 patients diagnosed with MBC in the database, 252 (1%) met the eligibility criteria. All patients were female. The median age was 56.6 years; 149 patients (59%) were diagnosed with de novo MBC; 248 (98%), with estrogen receptor-positive disease; and 182 (72%), with progesterone receptor-positive disease. One hundred ninety-three patients (77%) received an aromatase inhibitor as ET. The median number of taxane cycles received prior to the index date was six. Median maintenance rwPFS was 21.4 months (95% confidence interval = 16.1, 25.3). Conclusions: Given the therapeutic opportunity presented by HER2/HR co-expression and the favorable maintenance rwPFS shown here with PH + ET following taxane induction, the investigation of more potent ETs combined with PH is justified in order to further improve outcomes in first-line HER2-positive/HR-positive MBC.
Variations in Ewing sarcoma and rhabdomyosarcoma patient outcomes based on treatment center volume.
Authors: Sarah Yeo, Ying Hui Xu, Ursula Joan Yu Min Lee, Christine E. Simmons, Alannah Smrke, Ying Wang
Journal: Journal of Clinical Oncology (2022)

e18530 Background: Due to their rarity and requirement for multi-modality care, evidence suggests (and guidelines recommend) patients (pts) with Ewing Sarcoma (ES) and rhabdomyosarcoma (RMS) treated at high volume centres (HVC) with multidisciplinary tumour board discussions (MTDs) have improved outcomes. However, access to care at HVC is challenging for pts who live remotely, such as many pts in British Columbia (BC), Canada. Our study explores the difference in outcomes of patients with ES and RMS based on location of diagnosis and treatment in BC. Methods: A multi-center retrospective chart review of adults diagnosed with ES and RMS Jan 1 st 2000 to Dec 31 st 2020 was performed for pts undergoing curative intent therapy at one of six provincial cancer centers. All pts underwent expert pathology review. Descriptive statistics were performed. Fisher’s exact and chi-squared tests were used to evaluate associations. Cox proportional hazards model was used to assess for predictors of better survival outcomes by treatment centre. HVCs was defined as those that saw ≥15 patients. Results: 77 patients were included in this analysis; 46 (60%) and 31 (40%) were treated at HVC and LVC respectively. By HVC and LVC respectively, mean age was 36 and 35, 14 (45%) and 20 (43%) were female, 23 (74%) and 26 (57%) had ES, and 11 (35%) and nine (20%) had localized disease. Pts treated at HVCs were more likely to: receive curative intent radiation (p = 0.006), be presented at MTDs (p = 0.042), and less likely to experience disease progression on fist line therapy (p = 0.04) (Table). Time from biopsy to start of chemotherapy (chemo) was 13 days sooner at HVCs vs LVCs (34 vs 47 days, p = 0.12). Initial chemo regimen (p = 0.25) and surgical treatment (p = 0.75) were not significantly different between HVCs vs LVCs. Age, ECOG, stage, and Charlson Comorbidities Index (CCI) were all significant contributors to overall survival (OS). There was no statistically significant difference in OS by treatment center (HR 0.68, 95% CI 0.36 – 1.29). Conclusions: Variations in care exist for both treatment and outcomes amongst ES and RMS pts treated at HVC vs LVC in BC. Pts treated at HVCs were more likely to be presented at MTDs, to receive curative intent radiation, and less likely to experience disease progression. This may reflect differences in access to resources, sarcoma-specific clinician specialists, and familiarity with upfront aggressive treatment protocols. This study can be used to better inform decisions regarding triaging and centralization of curable ES and RMS patients.[Table: see text]
First interim analysis of the SirTac trial: A randomized phase II study of SIRT and DSM-TACE in patients with liver metastases from uveal melanoma.
Authors: Caroline-Anna Anna Peuker, Maximilian De Bucourt, Bernhard Gebauer, Holger Amthauer, Christoph Erxleben, Jan Eucker, Ulrich Keller, Serge Leyvraz, Antonia M. Joussen, Ulrich Keilholz, Sebastian Ochsenreither
Journal: Journal of Clinical Oncology (2022)

9511 Background: The liver is the most common site of metastases in patients (pts) with uveal melanoma (UM). Here, we present results from the prespecified first interim analysis of the SirTac trial, a prospective, single-center, randomized, investigator-initiated, open-label phase 2 study of Selective Internal Radiation Therapy with Yttrium-90-bearing resin microspheres; SIR-Spheres (SIRT) vs Transarterial Chemoembolization with Cisplatin and degradable starch microspheres; EmboCept S (DSM-TACE) in pts with liver-dominant metastatic UM. Methods: Pts with histologically confirmed, liver-dominant metastatic UM and ECOG PS 0-2 were enrolled and randomized 1:1 to SIRT or DSM-TACE. Randomization was stratified by lactate dehydrogenase (&lt;2x vs ≥2x upper limit of normal) and pre-treatment with antiangiogenic agents. Extrahepatic metastases were allowed, if asymptomatic. Primary endpoint was progression-free survival (PFS). A total of 108 pts (54 per arm) were planned to be enrolled. Pts received TACE every 4-6 weeks until tumor devascularization or disease progression or intolerable toxicity was observed, and SIRT either as one whole-liver application or in two sequential sessions for each liver lobe. The primary objective of this prespecified analysis was to assess response by RECIST criteria v1.1 in the per-protocol (PP) population of the first 40 pts (20 pts in each arm). Results: Two patients had been treated with previous liver surgery, whereas all other patients had not received previous treatment for metastatic disease. There were no clinicopathological differences between the groups, except for a difference in age (median age SIRT arm 64 y vs 75 y in the TACE arm, p=0.018). All but 1 pt received treatment as randomized. This pt was excluded and replaced by the next TACE pt for this PP interim analysis. There were no differences in best overall response rates between the groups (no complete response, 1 partial response in both arms, stable disease in 19 (95%) and 17 (85%) pts in the SIRT and TACE arm, respectively, and 2 pts with progressive disease in the TACE arm). At a median follow-up of 13.9 mo from treatment start, median PFS in the PP population was 4.9 mo in the SIRT arm vs 2.2 mo in the TACE arm (p=0.037), with a higher median liver-PFS in the SIRT vs TACE arm (8.3 vs 2.2, p=0.026). Conclusions: In this planned interim analysis treatment in both arms was feasible with no differences in response. The explorativePFS analysis allows no conclusions on the final outcome after completion of the trial. The study continues recruitment. Clinical trial information: NCT02936388.
Body weight (BW) response timing to anamorelin (ANAM) in advanced non–small cell lung cancer (NSCLC)–associated cachexia.
Authors: Richard J.E. Skipworth, Declan Walsh, Daniela D. Rotaru, Gianluca Ballinari, David C. Currow
Journal: Journal of Clinical Oncology (2022)

12110 Background: BW loss and anorexia are key clinical manifestations of cancer cachexia, a multifactorial syndrome affecting around 80% of patients (pts) with advanced cancer. BW loss is associated with reduced tolerance and response to cancer therapy, and shorter survival. ANAM is a novel, oral selective ghrelin receptor agonist. In ROMANA 1 and 2 (NCT01387269, NCT01387282) studies in pts with NSCLC and cachexia, ANAM treatment significantly increased BW and improved anorexia symptoms and concerns compared with placebo (PBO), with rapid responses occurring at wk 3 and sustained at wk 6, 9, and 12. In this post-hoc analysis, we report the timing of BW responses to assess the effects of ANAM treatment at and beyond wk 3. Methods: In ROMANA 1 and 2, pts with advanced NSCLC and BMI &lt;20 kg/m 2 or BW loss ≥5% in the past 6 mo received ANAM or PBO for 12 wk. BW responses were grouped on the basis of BW change from baseline (BW gain 0 to &lt;5% or ≥5%, and BW loss); pts were classified according to the timing of first BW response as early responders (at wk 3), late responders (at wk 6, 9, or 12), and non-responders. Missing values were not imputed. Categorical variables are presented as number and percentages, with statistical comparisons performed using the chi-square test. Results: In total, 552 pts in the ANAM arm and 277 in PBO were included in the analysis for all time points; at wk 3/6/9/12, data were available for 534/520/461/412 pts in the ANAM arm and 270/262/229/206 in PBO. The non-cumulative rate of pts with BW gain ≥5% was significantly higher with ANAM compared with PBO at wk 3 (13 vs 6%, p=.0030), wk 6 (26 vs 8%, p&lt;.0001), wk 9 (28 vs 9%, p&lt;.0001), and wk 12 (31 vs 11%, p&lt;.0001); conversely, the rate of BW loss was significantly lower with ANAM at all time points (p&lt;.0001). There were no significant differences between ANAM and PBO in the rate of pts with BW gain 0 to &lt;5% at wk 3, 6, 9, and 12 (p≥.0500). The timing of first occurrence of ≥5% BW gain response is shown in the table. The rates of early and late responders were significantly higher with ANAM compared with PBO, with 28% of ANAM-treated pts first responding beyond wk 3; a larger proportion of responses with ANAM were sustained over time. Conclusions: ANAM significantly increased the rates of ≥5% BW gain and reduced BW loss rates compared with PBO at all time points; the proportion of first responders at wk 3 and beyond wk 3 was higher with ANAM, with the most significant increase seen at wk 6. Continuing ANAM treatment beyond wk 3 results in a clinically significant benefit. Clinical trial information: NCT01387269, NCT01387282. [Table: see text]
A phase II study to evaluate the safety and efficacy of anlotinib combined with toripalimab for advanced biliary cancer.
Authors: Jie Shen, Weiwei Kong, Sihui Zhu, Baorui Liu
Journal: Journal of Clinical Oncology (2022)

4077 Background: To evaluate anlotinib combined with toripalimab for advanced biliary cancer that failed or without the will of standard first-line treatments. Methods: Open single arm phase II study were conducted, eligible patients (pts) were advanced biliary without the chance of operation and failed or without the will of standard first-line treatments. Pts received anlotinib 12mg po qd in 21-day cycles and toripalimab 240mg i.v. every 3 weeks. The main outcome measure was the objective response rate (ORR) of the target lesions evaluated by researchers based on the RECIST 1.1 standard, the secondary outcome measures were progress free survival (PFS) and treatment-related adverse event (TRAE). Results: As of Jan, 2022, 15 pts were enrolled including 9 the intrahepatic cholangiocarcinoma, 3 hilar Cholangiocarcinoma, and 3 the gall bladder carcinoma. 11 (73.3%) pts failed standard first-line treatments, and 4 pts were without the will of standard first-line treatments. The median follow-up was 254 days and 15 pts were all evaluated. 4PR, 9SD and 2PD were achieved. The ORR and DCR for irradiated target lesions was 26.7% and 86.7%, respectively. PFS for first line treatment was 139 days, and for second line treatment as 171 days. By this strategy, 1 ps was successfully transferred to operation after 3 cycle treatment. TRAEs (all grades) occurred in 14 (93.3%) pts. Grade 3 related AEs were fatigue (13.3%). Grade 1-2 related AEs were white blood cell count decreased (53.3%), hypertension (20.0%), thrombocytopenia (60.0%), fatigue (13.3%), hypothyroidism (6.7%), and fever asthenia (6.7%). Conclusions: The combination of anlotinib and toripalimab were demonstrated promising anti-tumor activity in advanced biliary cancer. Clinical trial information: ChiCTR2000037847.
Genetic alteration profiling of Chinese lung adenocarcinoma: A targeted and immunotherapy biomarker analysis.
Authors: Zhiqiang Zou, Phuong Anh Nguyen Thi, Chaoran Xia, ShouTai Ding, Peng Luo
Journal: Journal of Clinical Oncology (2022)

e20572 Background: Lung adenocarcinoma is the most common primary lung cancer, comprises about 30% of lung cancers. So far, little is known about an in-depth molecular characterization for lung adenocarcinoma in Chinese patients. The genomic characteristics, microsatellite instability (MSI) status, programmed cell death-1 (PD-L1) and tissue tumor mutational burden (tTMB) in Chinese lung adenocarcinoma patients will benefit to understanding drug resistance-related mechanisms. Methods: 591 Formalin-Fixed Paraffin-Embedded (FFPE) lung adenocarcinoma samples were collected and detected by Next Generation Sequencing 603-gene panel. The biomarkers of immunotherapy (TMB-High [≥10/Mb], MSI-High, and PD-L1 22C3 [TPS] were also calculated. Results: Of 591 patients, 312 patients (52.8%) were male and 279 (47.2%) patients were female. The median age of the patients was 60.7 (range 28-99). The most commonly mutated genes were EGFR (45.5%), TP53 (22.1%), KRAS (7.8%), PIK3CA (5.3%), ERBB2 (2.5%), BRAF (2.2%), CTNNB1 (1.5%), SMAD4 (1.5%),NRAS (1.0%), SMAD4 (1.5%), NRAS (1%), ATM (1%), RB1 (1%), NF1(1%), IDH2 (0.67%). Three genes mutations (EGFR, TP53, KRAS) were identified significantly different between male and female. EGFRmutations were significantly more frequent in females (54.12%) than in males (37.5%;p = 0.000051). In contrast, TP53 mutations were significantly more frequent in males (11.53%) than in females. KRASmutations were significantly more frequent in males (25.6%) than in females (17.9%;p = 0.023). (3.6%;p = 0.0003). The aging of patients was associated with a higher PTEN mutations (&lt; 50 years-old, p = 0.039), RAF1 mutations (&gt; 76 years-old, p = 0.038), BRCA1 mutations (&lt; 42 years-old, p = 0.032). The average of TMB was 5.3 mut/Mb (range 0-54.8). Immunotherapy markers were presented in 36.4% of cases (TMB-High in 15.91%, PD-L1+(TPS &gt; 1%) in 47.12%,PD-L1+(TPS &gt; 50%) in 5.17%, MSI-High in 0.17%). PD-L1 expression and TMB score were not significantly correlated in lung adenocarcinoma. The TMB score was associated with a higher TP53 mutations(TMB &gt; 6.6, p &lt; 0.0001), KRAS(TMB &gt; 6.1, p = 0.034), NF1(TMB &gt; 9.8, p = 0.0018), IDH2(TMB &gt; 11.3, p = 0.0028). Conclusions: These findings may be helpful for identifying therapeutic targets strategies in lung adenocarcinoma patients that were previously unavailable to clinicians in China.
The decline of circulating tumor cell clusters count for predicting the treatment response in breast cancer patients.
Authors: Hsu-Huan Chou, Ting-Fang Che, Shin-Cheh Chen, Chi-neu Tsai, Ying Chang, Fang Ming Chen
Journal: Journal of Clinical Oncology (2022)

e13009 Background: Circulating tumor cells (CTCs) are the precursors of metastatic cancer because they originate from primary tumor sites into the vascular system. The prognostic information of CTCs was well established in breast cancer treatment while the predictive value was still unclear. The aim of this study was to analyze the predictive value of CTCs count during treatment. Materials and Methods: A prospective study was conducted from 2019 to 2021, and 31 female breast cancer patients were enrolled, and 54 blood samples were collected at Linkou Chang Gung Memorial Hospital. The median age was 47 years old. We used LIPO platform for CTC isolation with anti-EpCAM antibody. To achieve maximum cellular viability, the LIPO platform was further optimized by using liposomes-lipid bilayers instead of lipid bilayers as the underneath surface coating to facilitate the detachment of bound cells from the surface and maintain cellular viability. Results: Fourteen patients were Stage II or stage III (non-metastasis) and 17 metastatic patients were included. Eleven patients (35.5%) were ER-positive HER2-negative while 10 patients (32.6%) were ER-positive HER2-positive. Three patients (9.7%) were HER2 enriched subtypes, and 7 patients (22.6%) were triple negative breast cancer. Blood samples from a total of 28 patients can be analyzed. At least one CTC was detected in 44/49 (89.8%) blood samples, CTC can’t be identified in 2/5 (40%) post-treatment with good response. The average single CTC count per 2 ml was 34.40 in non-metastatic patients versus 110.43 in metastatic patients (p = 0.3895). The average clustered CTC count per 2 ml was 13.44 in non-metastatic patients versus 40.16 in metastatic patients (p = 0.424). The total single and clustered CTC count per 2 ml was 47.84 non-metastatic patients versus 150.59 in metastatic patients (p = 0.3977). In 10 patients with clinically partial response, the average single CTC count per 2 ml was 61.9 before treatment and 11.81 after treatment (p = 0.0716), and the average clustered CTC per 2 ml was 15.83 before treatment and 5.28 after treatment (p = 0.8806). In 4 patients with clinical progression, the average single CTC count per 2 ml was 22.694 before treatment and 26.125 after treatment (p = 0.0257), and the average clustered CTC per 2 ml was 7.69 before treatment and 16.61 after treatment (p = 0.3798). Conclusions: Our findings concluded that the decline of circulating tumor cell clusters count can predict the treatment response in breast cancer patients.
Variable detection of actionable alterations across racial groups and association with testing patterns.
Authors: Emma Sturgill, Jessica Correia, Cooper Schumacher, Daniel Luckett, Suzanne Fields Jones, Howard A. Burris III, David R. Spigel, Andrew Jacob McKenzie
Journal: Journal of Clinical Oncology (2022)

3116 Background: Molecular landscape studies are critical to biomarker discovery and precision oncology research. However, non-White patients (pts) have historically been under-represented. In this study, we examine clinico-genomic data from a network of community oncology clinics to evaluate real-world mutational frequencies in Black, White, and Asian pts with cancer. Methods: We utilize Genospace, a precision medicine software, to harmonize clinical data from the Sarah Cannon research network of U.S. community oncology practices with genomic data from commercial NGS vendors. Pts with known race and NGS test results from September 2015 to November 2021 are assessed. Variants of uncertain significance (called by NGS vendor) are excluded. Asian pts are not evaluable in all instances because of low pt number. Statistical analyses include Chi squared and two sample test of proportions with Benjamini-Hochberg false discovery rate correction. Results: A total of 18,399 pts are assessed, with 7% Black (n = 1,319), 92% White (n = 16,903), and 1% Asian (n = 177) pt representation. The most common tumor types include non-small-cell lung (NSCLC; 27% of Black pts, 30% of White pts, 33% of Asian pts), colorectal (15% of Black pts, 12% of White pts, 14% of Asian pts), breast (14% of Black pts, 11% of White pts, 9% of Asian pts), and prostate (6% of Black pts, 5% of White pts, 3% of Asian pts) at roughly equal proportions across racial groups. In NSCLC, EGFR mutations and ALK fusions significantly enrich in Asian pts while KRAS G12C is detected more frequently in Black patients (see table for details; Black: n = 353, White: n = 5,127, Asian: n = 58). In both prostate and breast cancers, plasma-based NGS is less common in Black pts than White pts (plasma-to-tissue ratio = 1.1 (Black prostate: n = 82); 1.5 (White prostate: n = 863); 0.6 (Black breast: n = 178); 0.9 (White breast: n = 1,918)). In prostate, AR mutations are detected less frequently in Black pts. However, when considering plasma-NGS results alone the detection frequency is roughly equal. Similarly, the gap in ESR1 detection frequencies in breast decreases when considering plasma-NGS results alone. Conclusions: Actionable alterations are detected across racial groups at variable frequencies with potential biological and technical underpinnings. In scenarios where plasma-NGS is commonly used to monitor for resistance mutations, discrepancies in NGS ordering patterns likely affect detection frequencies. [Table: see text]
Cardiovascular disease in testicular cancer survivors: Identification of risk factors and impact on quality of life.
Authors: Sjoukje Lubberts, Harmke J. Groot, Ronald De Wit, Sasja F. Mulder, Alfred Alfred Witjes, Jan M. Kerst, Gerard Groenewegen, Joop D. Lefrandt, Flora Van Leeuwen, Janine Nuver, Michael Schaapveld, Jourik A. Gietema
Journal: Journal of Clinical Oncology (2022)

12070 Background: Testicular cancer (TC) treatment has been associated with cardiovascular disease (CVD) development. To facilitate development of preventive strategies, this study assessed risk factors associated with CVD in TC survivors. Methods: Incidence of coronary artery disease, myocardial infarction and heart failure was assessed in a multicenter cohort comprising 4,748 TC survivors treated at ages of 12-50 years between 1976-2007. Patients who developed CVD and a random sample from the cohort received a questionnaire on cardiovascular risk factors (CVRF) and quality of life (QoL, measured with SF-36). A subgroup (n=304) of responders in the cohort additionally underwent clinical evaluation of CVRF. Results: After a median follow-up of 16 years, 272 patients developed CVD. Compared to orchidectomy only, platinum-based chemotherapy was associated with increased CVD risk (Hazard Ratio (HR) 1.8, 95% Confidence Interval(CI) 1.3-2.5). CVD risk was increased among patients who were obese or a smoker at diagnosis (HR 4.7, 95%CI 2.4-9.3 and HR 1.5, 95%CI 1.1-2.2, respectively) and patients with Raynaud's phenomenon (HR 1.9, 95%CI 1.1-3.6) or a family history of CVD (HR 2.7, 95%CI 1.6-4.5). TC survivors with CVD reported inferior QoL on physical domains (table). In TC survivors who underwent clinical evaluation for CVRF (median age at assessment 51 years), 86% had dyslipidemia, 50% hypertension and 35% metabolic syndrome, irrespective of treatment. Conclusions: TC survivors treated with platinum-based chemotherapy, who were obese or smoking at diagnosis, had family history of CVD and who developed Raynaud’s phenomenon are at risk to develop CVD, which affects QoL. Many TC survivors carry undetected CVRF. We advocate early lifestyle adjustments and lifelong follow-up with low-threshold treatment of CVRF, especially in obese and smoking patients treated with platinum-based chemotherapy. [Table: see text]